Epitopes described in "CTL responses of HLA-A2.1-transgenic mice specific for hepatitis C viral peptides predict epitopes for CTL of humans carrying HLA-A2.1."

Article Authors:M Shirai; T Arichi; M Nishioka; T Nomura; K Ikeda; K Kawanishi; V H Engelhard; S M Feinstone; J A Berzofsky
Article Title:CTL responses of HLA-A2.1-transgenic mice specific for hepatitis C viral peptides predict epitopes for CTL of humans carrying HLA-A2.1.
Reference Detail
Reference ID:315039
Abstract:Vaccine development in animal models depends on ability to recognize epitopes seen by human T cells. In this work, we show that CTL responses in transgenic mice expressing human HLA-A2.1 prospectively predict the same four of 11 hepatitis C virus (HCV) structural protein-derived peptides, expressing a sequence motif for HLA-A2.1 binding, that are actually recognized by human A2.1-restricted CTLs. The CTLs also recognized targets endogenously expressing these proteins. Human CTLs from HCV-infected patients, tested by using the same peptides, revealed a virtually identical response repertoire. A highly conserved HCV core peptide was the most immunogenic, and may be a valuable component of a vaccine against a broad range of HCV isolates in HLA-A2-positive patients. These results suggest that, in spite of species differences, the T cell repertoire is plastic enough to allow a similar response when the same class I MHC molecule is presenting the peptide. Thus, the HLA molecule plays the primary role in determining which peptides are recognized by CTLs. This transgenic mouse model is important for the study of HLA-restricted CTL determinants and for an approach to design a potential HCV vaccine.
Affiliations:Third Department of Internal Medicine, Kagawa Medical School, Japan.
Reference Type:Literature
PubMed ID:7533182
Journal:J Immunol
Journal Volume:154
Article Pages:2733-42
Journal ISSN:0022-1767
Article Chemical List:Antigens, Viral;Epitopes;HLA-A2 Antigen;Hepatitis C Antigens;Receptors, Antigen, T-Cell;Recombinant Proteins
Article MeSH List:Adult; Aged; Amino Acid Sequence; Animals; Antigens, Viral(immunology); Cytotoxicity Tests, Immunologic; Epitopes(immunology); Female; HLA-A2 Antigen(genetics; immunology); Haplotypes(immunology); Hepacivirus(immunology); Hepatitis C Antigens; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Molecular Sequence Data; Receptors, Antigen, T-Cell(immunology); Recombinant Proteins; T-Lymphocytes, Cytotoxic(immunology)
Article Comments:Data originally imported from the Database of Functional Molecular Immunology, FIMM (http://sdmc.lit.org.sg:8080/fimm/)
Curation Last Updated:2015-07-24 20:01:47